title: Inflammatory adipokines contribute to insulin resistance in active acromegaly and respond differently to different treatment modalities.
abstract: BACKGROUND
  Active acromegaly is associated with insulin resistance, but it is uncertain whether inflammation in adipose tissue is a contributing factor.
  
  
  OBJECTIVE
  To test if GH/IGF1 promotes inflammation in adipocytes, and if this is relevant for systemic insulin resistance in acromegaly. Furthermore, to investigate the effect of treatment modalities (transsphenoidal surgery (TS), somatostatin analogs (SAs), and pegvisomant (PGV)) on glucose metabolism and inflammatory biomarkers in acromegaly.
  
  
  METHODS
  The in vitro effects of GH/IGF1 on gene expression of adipokines in human adipocytes were investigated. Body composition, glucose metabolism, and circulating adipokines (adiponectin (AD), high-molecular weight AD (HMWAD), leptin, vascular endothelial growth factor-A (VEGF-A), monocyte chemotactic protein 1 (MCP1), and thioredoxin (TRX)) were measured in 37 patients with active acromegaly before and after treatment.
  
  
  RESULTS
  In vitro GH, but not IGF1, increased VEGF and MCP1 in human adipocytes. In all treatment groups, body fat increased and IGF1 decreased to the same extent. Fasting glucose decreased in the TS (P=0.016) and PGV (P=0.042) groups, but tended to increase in the SA group (P=0.078). Insulin and HOMA-IR decreased in both TS and SA groups, while the PGV group showed no changes. Serum VEGF and MCP1 decreased significantly in the TS group only (P=0.010, P=0.002), while HMWAD increased with PGV treatment only (P=0.018). A multivariate analysis model identified the changes in GH and VEGF as predictors of improvement in HOMA-IR after treatment (R²=0.39, P=0.002).
  
  
  CONCLUSIONS
  i) GH directly promotes inflammation of human adipocytes by increasing VEGF and MCP1 levels; ii) glucose metabolism and inflammation (VEGF and MCP1) improve to some extent after treatment, despite an increase in adipose tissue mass; and iii) the decrease in insulin resistance after therapy in acromegaly depends, to some extent, on treatment modalities.
authors.affiliation: Section of Specialized Endocrinology, Department of Endocrinology.
authors.forename: Nicoleta C
authors.initials: NC
authors.lastname: Olarescu
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.forename: Kristin
authors.initials: K
authors.lastname: Godang
authors.forename: Rune
authors.initials: R
authors.lastname: Lindberg-Larsen
authors.forename: Jens Otto L
authors.initials: JO
authors.lastname: Jørgensen
authors.forename: Jens
authors.initials: J
authors.lastname: Bollerslev
mesh_terms: D000172:Acromegaly / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000601:surgery; D050154:Adiposity / Q000187:drug effects; D000328:Adult; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000097:blood / Q000235:genetics / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D019382:Human Growth Hormone / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000031:analogs & derivatives / Q000627:therapeutic use; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000378:metabolism; D013004:Somatostatin / Q000031:analogs & derivatives / Q000627:therapeutic use; D050151:Subcutaneous Fat / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000235:genetics / Q000378:metabolism
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D018836:Inflammation Mediators; D011994:Recombinant Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C541923:sandostatinLAR; D019382:Human Growth Hormone; D013004:Somatostatin; C406545:pegvisomant; D015282:Octreotide